Structure-activity relationships are reported for a novel class of 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid derivatives that displace 125I-labeled angiotensin II from a specific subset of angiotensin II (Ang II) binding sites in rat adrenal preparations. This binding site is not the Ang II receptor mediating vascular contraction or aldosterone release, but, rather, is one whose function has not yet been fully elucidated. It has been identified in a number of tissues and has a similar affinity for Ang II and its peptide analogues as does the vascular receptor. The non-peptide compounds reported here are uniquely specific in displacing Ang II at this binding site and are inactive in antagonizing Ang II at the vascular receptor or in pharmacological assays measuring vascular effects. PD 123,319 (79), one of the most potent compounds, has an IC50 of 34 nM. Certain of these compounds may have utility in the definition and study of Ang II receptor subtypes.

as from a Soxhlet extraction. Analysis of AA, AB, and BB ratios were carried out by using a Varían Aerograph 3700 gas chromatograph. To check for possible interconversion of AA, AB, and BB on the zeolite, a known mixture of AA, AB, and BB (obtained via photolysis of 4-MeDBK in benzene) was deposited on the zeolites and reextracted via the above described procedures. Interconversion of AA, AB, and BB was not observed on any of the zeolites. A 5-10% loss of AA was observed on Silicalite, but % CE's are only affected by <4% due to this "preferential adsorption" of AA. Thus, no corrections were applied to the apparent % CE's observed for Silicalite.13C-Enrichment Studies. DBK-13C (2') was deposited on zeolites and photolyzed in the same manner as described above. 13C-Content was determined by mass spectrometry using a Finnegan 3300 GC/MS system (SE-30 column; multiple ion detection mode). The details in calculating a are available elsewhere.21"25 The identity of PMAP was confirmed by coinjection with an authentic sample of the compound. An additional isomer (as determined by its mass spectrum) (~1%) was observed on photolysis in Na+-X, and is believed to be the ortho analogue of PMAP. However, due to the low yield observed, direct confirmation of its structure was not feasible. Conversions were >80% for all the zeolites except Silicalite, in which case <30% conversion was used. We found that it was not possible to take Silicalite to high conversion. The probable reason for this is that homogeneous tumbling of Silicalite samples proved to be problematic due to the extreme powdery form of the sample.Adsorption Isotherms. For adsorption isotherm studies, 2,2,4-trimethylpentane (isooctane) was chosen as the solvent since it is known that the kinetic diameter is >6.2 Á based on the fact that for neopentane, the kinetic diameter is 6.2 Á.14•16 A preweighed amount of DBK dissolved in 30 mL of isooctane was added to 100 mg of zeolite and stirred rigorously with a magnetic stirring bar at room temperature (25 ± 3 °C) for 15 h. The slurry was then filtered by using a microfiltration apparatus, and dodecane internal standard was added. After removal of most of the solvent, the mixture was analyzed for DBK content via GLC (capillary SE-30 column; Varían Aerograph Model 3700). The amount of DBK adsorbed was calculated by taking the difference of the amount of DBK exposed to the zeolite and the amount recovered in the solvent filtrate. Decomposition of DBK was not observed during the period of the experiment.to Dr. Edith Flanigen, Union Carbide Corp., Tarrytown, NY, for stimulating discussions concerning zeolite structure and catalysis and their potential use in organic photochemistry. Dr. Chao Chung is thanked for performing some initial, exploratory investigations.Registry No. 1, 2,

Super-resolution microscopy enables imaging of structures smaller than the diffraction limit. Single-molecule localization microscopy methods, such as photoactivation localization microscopy and stochastic optical reconstruction microscopy, reconstruct images by plotting the centroids of fluorescent point sources from a series of frames in which only a few molecules are fluorescing at a time. These approaches require simpler instrumentation than methods that depend on structured illumination and thus are becoming widespread. The functionalized rhodamine derivative reported in this paper spontaneously converts between a bright and dark state due to pH-dependent cyclization. At pH 7, less than 0.5% of the dye molecules are fluorescent at any given time. Blinking occurs on time scales of seconds to minutes and can therefore be used for single-molecule localization microscopy without sample treatment or activation. The dye is bright and straightforward to use, and it is easy to synthesize and functionalize. Thus, it has potential to become a new and powerful addition to the toolset for super-resolution imaging.

A series of renin inhibitors having alpha-heteroatom amino acids as P2 substitutions has been prepared. Examples where the heteroatom is oxygen, sulfur, or nitrogen are described. Many of the compounds exhibit subnanomolar potency when tested in vitro against monkey renin. When selected compounds were tested orally in conscious, salt-depleted, normotensive, Cynomolgus monkeys, low to moderate blood pressure lowering was observed. At an oral dose of 30 mg/kg, compound 53a lowered blood pressure by a maximum of 18 mmHg at 2.5 h post-dose.

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